1. Field of the Invention
This invention relates to a method of separating cineoles, and more particularly, to a method of separating 1,4 cineole from a mixture of 1,4 and 1,8 cineoles by use of a zeolite molecular sieve. The structural formulas for 1,4 and 1,8 cineoles are shown below. ##STR1##
Cineoles (also known as eucalyptols) have been found to have a wide variety of uses. Muller, et al. have discovered that cineole may be used to retard the respiration of herb roots and inhibit the growth of seedlings. Bull. Torrey Bot. Club 1968, 95(5), 415-22.
Dassler and Dube found that 1,4 cineole was a useful insecticide for use against flies, 1,8 cineole, however, was useful against bark-beetles, but did not show the same results against flies, Anz. Schadlingskunde 30, 86-8(1967).
Dodson, et al. have described 1,8 cineole as an attractant for male euglossine bees. The 1,8 cineole was found to be a component in orchid fragrances. Science 1969, 164(3885), 1243-9.
Cineoles also have uses as medicinal compositions. This is shown by Pozzo, et al. who describe a method of determining the amount of eucalyptol in pharmaceutical syrups and suppositories. Boll. Chim. Farm. 1969, 108, 47-56. Stamm, et al. describe the optimization of retaining eucalpytol by use of different absorbents in compressed tablets. Bull Soc. Pharm. Strasbourg 1970 13(2) 89-95.
In Ger. Offen. No. 2,213,993 Sept. 27, 1973) and British Pat. No. 1,343,561, Igimi et al. described essentials oils which were found to be useful in dissolving gallstones in bile liquid. Cineole was listed as an example of one of these essential oils. French Pat. No. 1,495,547 describes eucalpytol as a useful component in compositions for regulating the activity of sebaceous glands. Lobel, U.S. Pat. No. 3,105,793, includes eucalyptol in a composition useful for reducing the side effects of injectable antibiotics. Cineole has been found to inhibit the oxygen uptake by mitochrondria of seedlings. Bull. Torrey Bot. Club 1969, 96(1), 89-96.
More importantly, eucalyptol has been found to effect the metabolism of drugs in humans. Eur. J. Pharmacol, 1970, 9(3), 326-6; Biochem. Pharmacol. 1969, 18(9), 2081-5. These metabolic effects can be very important in the detoxification of certain compounds in humans.
Although mixtures of 1,4 and 1,8 cineoles may be useful, it is generally considered that the separated compounds are more valuable than the mixture. The difficulty in separating such mixtures can be seen by comparing some of the more important physical properties of the two compounds.
______________________________________ Property 1,4 cineole 1,8 cineole ______________________________________ Molecular weight 154.25 154.25 Boiling point (760mm Hg) 173-4.degree. C. 176.4.degree. C. Density 0.8997.sup.20 0.9267.sup.20 ______________________________________
Each cineole is practically insoluble in water and is miscible with alcohol, chloroform, ether, glacial acetic acid and other hydrocarbon solvents in general.
For further physical, chemical and pharmaceutical properties of cineoles, see Izvest, Akad. Nauk Kazakh. S.S.R. No. 118, Ser. Khim., No. 6, 90-106(1953).
Because of the similarities of the properties, it is apparent that conventional separation methods, such as distillation or phase separation, are not suitable for the separation of the cineoles.
Cineoles are generally prepared by treating bicyclic monoterpene hydrocarbons, dipentenes, or isoprenes with mineral acids such as sulphuric acid. Japanese Patent 68-24,674; Vestsi Akad. Navuk B. SSR, Ser. Khim. Navuk 1974, (5); 61-4; Vestsi Akad. Navuk B. SSR, Ser. Khim, Navuk 1974, (6), 17.varies.19; and Japanese Patent 68-24,186. These methods result in final mixtures containing similar amounts of 1,4 and 1,8 cineoles, along with other products such as menthadienes, cymenes and terpinenes. Cineoles are also available from natural sources, such as oils of wormwood and eucalyptus. Mixtures of cineole isomers can be synthetically obtained from limonene, terpin hydrates, turpentine and oil of turpentine.
2. Description of the Prior Art
Previous methods of separating mixtures of cineoles have been difficult and unwieldy. One process, described in Japanese Patent No. 69-07,340 (Mar. 31, 1969) by Matsuhara et al involves treating a crude mixture including 1,4 and 1,8 cineoles with thiourea. The 1,4 cineole then separates as an adduct. This process is limited to liquid phase operations.
U.S. Pat. Nos. 2,459,432 and 2,459,433, both to Johnson, disclose a method for separating cineoles from hydrocarbons. A cineole-containing hydrocarbon mixture is treated with phenol, resulting in three azeotropic mixtures which are separatable from each other by distillation: hydrocarbon and phenol; 1,4-cineole and phenol; and 1,8 cineole and phenol. The 1,8-cineole azeotrope boils higher than the 1,4-cineole azeotrope. Fractional steam distillation may be used to recover each of the cineoles from its respective azeotrope.
Davis, in U.S. Pat. No. 3,923,837 describes an extraction process for removing cineoles from a terpene fraction by use of a strong mineral acid, such as sulphuric. The cineoles are removed into the acid component. However, both 1,4 and 1,8 cineoles are removed by the acid extraction.
Okuda, Japanese Pat. No. 1172-50 describes isolating cineoles from other essential oils. 2-naphthol is added to white camphor oil and centrifuged. Sodium hydroxide is added to the formed compound, resulting in an oily layer which is steam-distilled to obtain the cineoles.